Dr. Braden is the product manger for both Jaguar and QSite. In this article, Dr. Braden discusses some of the new Jaguar and QSite features scheduled for Suite 2008.
Throughout our development of Jaguar, our quantum mechanics software program, and QSite, our mixed QM/MM program, we continue to enhance performance, ease of use, and to enable the calculation of new properties of interest to chemists. A significant new feature for the 2008 versions of both of these programs will be the ability to calculate vibrational frequencies, NMR shielding, and molecular polarizabilities for molecules surrounded by point charges. For Jaguar users, this means that these properties can be calculated while using the PBF solvation model. For QSite users, these properties will be available for the first time, and can be calculated with or without the PBF solvation model. Solvation can have a significant effect on many molecular properties, and because so many chemical reactions and measurements are carried out on solution phase samples, it is important to be able to use a solvation model when performing the calculation of molecular properties.
QSite
Ligand Vibrational Frequencies. In QSite the atoms of the receptor protein are represented by point charges which surround the ligand, which is in turn modeled quantum mechanically. One of the new 2008 features will make it possible for QSite users to calculate vibrational frequencies for the ligand. This is especially desirable when performing transition state searches to verify that the transition state has a single mode with the imaginary-valued frequency.
Below is a short movie clip illustrating this new feature. It shows one of the vibrations of adenosine while bound in the active site of human adenosine kinase. QSite, like Jaguar, can now write a file containing the vibrational data. Maestro can read this file and animate any of the vibrational modes.
QSite users will also be able to calculate NMR shielding for the nuclei of the ligand, and even polarizabilities up to second order. All of these properties can be calculated with or without the PBF solvation model. These properties are available for non-covalently bound ligands, and for QM regions for which the QM/MM boundary is defined using the hydrogen-cap method (also called the link-atom method). They are not available if the QM/MM boundary is defined using the frozen-orbital method.
Geometric Coordinate Scans. Another significant feature that has been added to QSite is the ability to perform geometric coordinate scans. This capability has been available in Jaguar for some time. QSite users will now be able to perform torsional scans of a docked ligand to explore how its flexibility is limited by its binding to the active site. It will also be easier to perform transition state searches for proton transfer reactions. In this case the high-energy point along the scan is also the transition state structure.
Jaguar
Increased Efficiency. Geometry scans in Jaguar have been made more efficient, such that scans of one or two coordinates can now be distributed across multiple processors. This is handled by a Python script which parses the input file and determines how many scan points will be generated. A new input file for each scan point is created, and the batch of jobs is then distributed across a number of processors of the user's choosing. This mode of operation provides for faster throughput than running the scan using MPI parallelism. The user can choose to use any number of processors up to the number of scan points, thus controlling both the Jaguar license usage and the processor resource usage.
pKa Predictor. The scope and robustness of Jaguar's pKa predictor have also been expanded for Suite 2008. For conformationally flexible molecules, different conformations can have significantly different pKa values, and the preferred conformations of the protonated and deprotonated species can also be different. It is therefore important to provide the best conformations as input for the pKa predictor. We have added a new, automated mode of operation which involves running a MacroModel conformational search on the protonated and deprotonated forms of the input structure (using a solvation model) in order to prepare the best input structures for the Jaguar pKa calculation. This feature is controlled by a simple toggle in the Jaguar pKa panel, so users can turn it off if they do not have MacroModel, or if they are confident that they already have the best conformations of the structure. Additionally, pKa correction factors for enols will be available in the Suite 2008 release of Jaguar.